Breast Cancer DOI 10.1007/s12282-014-0521-7

REVIEW ARTICLE

Meta-analysis of the effects of exercise intervention on quality of life in breast cancer survivors Yingchun Zeng • Meiling Huang • Andy S. K. Cheng Ying Zhou • Winnie K. W. So

•

Received: 5 November 2013 / Accepted: 3 February 2014 Ó The Japanese Breast Cancer Society 2014

Abstract Breast cancer is the most common type of cancer among women worldwide. Diagnosis and treatment of breast cancer pose an array of physical and psychological threats to the survivors. Exercise interventions may be particularly appropriate for cancer survivors because they have the potential to improve physical and psychological functioning. The review aims to examine the effectiveness of exercise intervention on the quality of life (QOL) of breast cancer survivors. Five databases (Medline, CINAHL, Scopus, The Cochrane Library, and CAJ Full-text Database) were searched from 2003 to July 2013. Clinical controlled trials of exercise interventions for breast cancer survivors who were at least 18 years old and had completed active cancer treatment were included. A total of 25 trials were included in this study, of which 19 were pooled

together statistically. Subjects in the exercise interventions had higher overall QOL than subjects in the control group. The standardized mean difference (SMD) for changes in overall general QOL scores was 0.70 (95 % CI 0.21, 1.19). The SMD for changes in cancer-specific QOL scores was 0.38 (95 % CI 0.03, 0.74). For cancer-specific QOL domains, there were positive but non-significant trends in two QOL domains (breast symptoms: Z score = 1.12, p = 0.26; arm symptoms: Z score = 1.32, p = 0.19). This study provides updated findings supporting the idea that exercise interventions have statistically significant effects on overall QOL in breast cancer survivors, as well as positive trends for cancer site-specific QOL domains (breast and arm symptoms). Keywords Breast cancer survivors
Exercise interventions
Quality of life
RCTs
Meta-analysis

Y. Zeng Department of Obstetrics, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China e-mail: [email protected] M. Huang (&) Department of Nursing, The Third Affiliated Hospital of Guangzhou Medical University, No. 63 Doubao Road, Guangzhou, China e-mail: [email protected] A. S. K. Cheng Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Kowloon, Hong Kong Y. Zhou School of Nursing, Guangzhou Medical University, Guangzhou, China W. K. W. So Nethersole School of Nursing, The Chinese University of Hong Kong, New Territories, Hong Kong

Introduction Breast cancer is the most common type of cancer among women worldwide. Over a million women are diagnosed with breast cancer annually. Breast cancer is responsible for 23 % of all cancer cases [1, 2]. Due to advances in medical technology and early detection, diagnosis of breast cancer has good prognosis, the relative 5- and 10-year survival rates for all stages are 90.6 and 81.5 % in the US [3], and 85.1 and 77 % in the UK [4]. Consequently, there is a substantial number of breast cancer survivors and there is an imperative for increased attention to their quality of survivorship [5]. Diagnosis and treatment of breast cancer could pose an array of physical and psychological threats to the survivors. These adverse outcomes from cancer and its treatment

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include cognitive impairment, chronic fatigue, weight gain, sexual dysfunction and infertility [6–9], all of which can impact the quality of life (QOL) of breast cancer survivors. In addition, significant treatment-related sequelae can be persistent for many years and continue to influence longterm quality of survival [10]. Current cancer care is increasingly being directed toward considering the quantity and quality of survival [5]. Therefore, there is a clear need to identify strategies for improving the length and quality of survival of breast cancer survivors. There has been widespread attention to the benefits of exercise on length of survival, health outcomes and promotion of quality of life in cancer populations [11]. Exercise interventions may be particularly appropriate for cancer survivors because they have the potential to improve physical and psychological functioning, including quality of life [12, 13]. Recent evidence suggests that regular physical exercise facilitates positive physiological and psychological health simultaneously in cancer survivors [14, 15]. Meanwhile, measuring quality of life and its domains can provide prognostic and predictive information for clinicians to understand women’s subjective survivorship experience and develop pertinent therapeutic and lifestyle interventions [16]. Although a Cochrane review examined the effects of exercise interventions among all types of cancer survivors [17], this review did not report the specific effects of exercise interventions on breast cancer survivors. While there have been two published meta-analyses of clinical trials of exercise interventions on the quality of life of breast cancer patients [14, 18], these two studies mainly focused on clinical trials of exercise intervention during active breast cancer treatment. Bicego and colleagues [19] conducted a systematic review of the effects of exercise on quality of life among a mixed study population of breast cancer patients and survivors, but this systematic review did not quantitatively clarify the effect of exercise intervention in women living with breast cancer. Duijts and colleagues [2] conducted a comprehensive meta-analysis of physical exercise and behavioral techniques on quality of life for both breast cancer patients and survivors, but this meta-analysis included randomized controlled trials up to March 2009. Since then, there have been more clinical trials of exercise interventions for breast cancer survivors. Thus, there is a need to conduct an updated meta-analysis of exercise intervention for this target study population.

Aims This study aims to determine the effectiveness of exercise interventions on overall QOL and domain-specific QOL in breast cancer survivors.

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Methods Data sources and searches Five databases (Medline, CINAHL, Scopus, The Cochrane Library, and CAJ Full-text Database) were searched from 2003 to July 2013, and articles published in English and Chinese were included in the sample. The search terms included ‘‘breast cancer,’’ ‘‘breast cancer survivors,’’ ‘‘exercise,’’ ‘‘physical exercise,’’ ‘‘aerobic exercises,’’ ‘‘physical activity,’’ ‘‘motor activity,’’ and ‘‘quality of life.’’ The process of study selection consisted of two steps: two researchers independently screened the titles and abstracts of the studies (ZYC, HML), and all potentially relevant studies that met the predefined inclusion criteria were included in the review. Disagreements were resolved by a third author (AC). Types of study and participants Studies were eligible for inclusion if they were clinically controlled trials that addressed the effects of physical exercise on the QOL of breast cancer survivors. In this review, cancer survivors were defined individuals who had completed active cancer treatment. Eligibility criteria for participants in those controlled trials included all stages of breast cancer survivors who were: at least 18 years old, had a diagnosis of breast cancer, and had completed active breast cancer treatment. Types of interventions and outcome measures Studies were included if they used any type of exercise (aerobic, anaerobic, or combined) with breast cancer survivors. ‘‘Exercise intervention’’ was defined in this metaanalysis as ‘‘a planned and systematically applied set of physical actions delivered in a specified setting and time to improve QOL for breast cancer survivors’’ [15]. Outcome measures included all QOL outcomes measured by generic (e.g., SF-36), cancer-specific (e.g., FACT-G, EORTC QLQ-C30), or cancer site-specific QOL scales (e.g., FACT-B, EORCT QLQ-BR23). Data extraction and assessment of risk of bias For each study, data were extracted from the original paper independently by one of the main researchers and then verified by another researcher. Disagreements about data extraction were resolved by discussion. Trial quality was judged based on the quality assessment method of the 2011 Cochrane Handbook. The Cochrane Risk of Bias Assessment Tool consists of seven domains: random sequence generation, allocation concealment, blinding of participants

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and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting, and other biases [20]. Data synthesis and analysis The Cochrane Collaboration’s Review Manager (RevMan 5.2) was used to generate pooled estimates of effect size [21]. Statistical heterogeneity was calculated with Chi square and I2 statistics. A Chi square with a p value greater than 0.1 and an I2 value of less than 50 % were considered indications of statistical homogeneity [16]. For continuous variables, mean difference (MD) was calculated when outcomes were measured using the same scale, and the standardized mean difference (SMD) was used when different scales were used in different trials, with corresponding 95 % confidence intervals (CIs) [20]. If data for standard deviations (SDs) were missing, they were computed for the calculation of statistical pooling of effect size by calculating the trail data using standard error of the mean or 95 % CIs [20]. Values of p \ 0.05 were considered statistically significant.

Results Description of included studies A total of 25 trials [5, 13, 22–44] were included in this study. The section of studies is shown in Fig. 1. Of these 25 trials, nineteen [5, 13, 23–27, 30–36, 40–44] provided enough data for statistical pooling. Table 1 summarizes the characteristics of these trials. Quality of study methods Each trial was evaluated in terms of its risk of bias (Fig. 2). Most (n = 18) had high risk of bias. Major sources of risk of bias were from lack of blinding study subjects or research personnel, incomplete outcome data and blinding of outcome assessment. Of 25 trials, only nine studies [5, 13, 23, 25, 28, 33, 36, 41, 43] described the method of randomization and eight studies [13, 20, 28, 30, 32, 33, 36, 43] described their methods of sequence generation or allocation concealment. Due to the nature of exercise intervention, it may be difficult to blind participants to intervention delivery. Few trials attempted to blind the outcome assessors to minimize potential methodological bias. Therefore, bias may affect most of the RCTs. Summary of exercise interventions The mode of exercise intervention included aerobic [13, 22–24, 27, 31, 32, 36, 37, 39, 40], a combination of aerobic

Fig. 1 PRISMA flow diagram of study selection

and anaerobic [29, 35, 38, 42], Yoga [21, 25, 33], Tai Chi [34, 43], aerobic and strength training [5, 28], aerobic and resistance training [41], and resistance training [26], resistance training and stretching [30]. The total duration of exercise intervention ranged from 4 to 52 weeks. Of the 25 studies, more than half (n = 15) had a total intervention duration ranging from 8 to 12 weeks. The frequency of intervention per week varied from 1 to 5 times per week. Time per session ranged from 15 to 90 min. Specific exercise intervention details are shown in Table 1. Effects of exercise interventions on QOL for breast cancer survivors Table 2 summarizes the results of the effects of exercise intervention on QOL. Six trials used generic QOL scales (e.g., SF-36, SF-12) to assess changes in generic QOL scores after exercise interventions. Figure 3 shows that the SMD was 0.70 (95 % CI 0.21, 1.19). For cancer-specific QOL measured either by the FACT-G or EORTC QLQ-30, Fig. 4 shows the improvement of cancer-specific QOL in favor of exercise intervention; its SMD was 0.38 (95 % CI 0.03, 0.74). For breast cancer-specific QOL measured by

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Breast Cancer Table 1 Summary of 25 clinical trials of exercise interventions for breast cancer survivors Trial

Study design

Study participants

Intervention

Outcome measure and assessment points

Outcome/results

Banasil 2011

RCT, pilot study

18 breast cancer survivors (C2 months’ post-treatment)

TG: 8-week group-based yoga intervention, twice per week, 90 min per session

FACT-B;

The yoga group improved emotional well-being and fatigue scores

Cadmus 2009

RCT

75 breast cancer survivors (C12 months’ post-treatment)

TG: 24-week supervised aerobic exercise intervention, 5 times per week, 30 min per session

Cho 2006

QuasiRCT

65 breast cancer survivors (C12 months’ post-treatment)

At baseline and at 8 weeks

CG: waitlist control

CG: usual care

TG: 10-week aerobic exercise intervention, twice per week, 90 min per session CG: waitlist control

SF-36 FACT-B CES-D; At baseline and at 6 months QOL and physiologic outcome measures; At baseline and at 10 weeks

Courneya 2003

Daley 2007

Danhauer 2009

RCT

RCT

RCT, pilot study

52 breast cancer survivors (posttreatment, time not reported)

108 breast cancer survivors (12–36 months’ post-treatment)

44 breast cancer survivors (C24 months’ post-treatment)

TG: 15-week aerobic exercise intervention, 3 times per week, 15–35 min per session CG: waitlist control

FACT-G

TG: 8-week supervised aerobic exercise, 3 times per week, 50 min per session

FACT-G FACT-B

CG1: exercise placebo

FACT-B FACT-F;

Exercise was not associated with QOL benefits, but exercise was associated with improved social functioning among post-treatment survivors who reported low social functioning at the baseline (p \ 0.05) Women in the TG had a significantly increased range of motion of the shoulder joint, and psychosocial adjustment and QOL, compared with women in the CG Overall QOL increased by 9.1 points in the TG compared with 0.3 points in the CG (p = 0.001)

At baseline and at 15 weeks

BDI aerobic fitness measures;

CG2: usual care

At baseline and at 8 weeks

TG: 10 weekly yoga sessions, once per week, 75 min per session

SF-12

CG: waitlist control

FACT-F

FACT-B

There was a significant mean difference of 9.8 units in FACT-G favoring aerobic exercise therapy. Significant differences that favored aerobic exercise therapy relative to usual care were also recorded for FACT-B Group differences favoring the yoga group were seen for mental health, depression, positive affect, and spirituality

FACIT-Sp CES-D; At baseline and at 10 weeks FernandezLao 2013

CCT

98 breast cancer survivors (posttreatment, time not reported)

TG1: 8-week supervised resistance training exercise program, 3 times per week, 60 min per session

EORTC QLQBR23

TG2: 8-week multimodal water exercise program, with 6-month follow-up

BMI;

CG: usual care

Fillion 2008

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RCT

94 breast cancer survivors (within 24 months’ post-treatment)

TG: 4-week aerobic exercise intervention, 4 times per week, 60 min per session CG: normal activity

BFI At baseline and at 8 weeks

SF-12 POMS; At baseline and at 12 weeks

Subjects in the land exercise group exhibited a greater decrease in percentage of body fat than those in the water exercise group (p \ 0.001) and the CG (p = 0.002); subjects in the water exercise group experienced a greater decrease of breast symptoms than those in the land exercise group (p \ 0.01) and the CG (p \ 0.05) Participants in the intervention group showed greater improvement in fatigue, energy level, and emotional distress at 3-month follow-up, and physical QOL at post-intervention, compared with participants in the CG

Breast Cancer Table 1 continued Trial

Study design

Study participants

Intervention

Outcome measure and assessment points

Outcome/results

Hayes 2013

RCT

194 breast cancer survivors (3–4 weeks’ post-treatment)

TG1: 32-week both aerobic and strength-based exercise intervention, 2–4 times per week, 45–90 min per session

FACT-B

There were significant (p \ 0.05) interaction effects on QOL, fitness, and fatigue with differences being observed between the TGs and the CGs

TG2: 32-week translational exercise intervention delivered by over-thetelephone follow-up CG: usual care Heim 2007

QuasiRCT

63 breast cancer survivors ([6 weeks’ post-treatment)

Herrero 2006

RCT

20 breast cancer survivors ([24 months’ post-treatment) 160 early stage breast cancer survivors (following posttreatment)

TG: intervention duration (not reported), aerobic exercise intervention, strength training 3 times per week and aerobic exercise for 30 min, twice per week

Fitness and upper body function Treatment-related side effects; at baseline, at 6 months and at 12 months FACIT HADS; at baseline and at 12 weeks

There was an improvement of muscle strength for both groups at the end of rehabilitation. The scores for global QOL increased from the baseline to the end of rehabilitation

TG: 8-week aerobic and anaerobic exercise intervention, 3 times per week, 90 min per session CG: usual activities

EORTC QLQ-C30

Combined cardiorespiratory and resistance training improved the QOL and the overall physical fitness of breast cancer survivors

TG: 8-week resistance training and stretching exercise program, once per week (time per session not reported) CG: usual care

EORTC QLQBR23

CG: waitlist control

Kilbreath 2012

RCT

Physiologic measures; At baseline and at 8 weeks

Physical measures of shoulder range of motion, strength, and swelling;

The changes in symptoms from the baseline were not significantly different between groups immediately at 6-month follow-up The change in range of motion for flexion and abduction was significantly greater in the TG

At baseline and at 8 weeks Mehnert 2011

RCT

63 breast cancer survivors ([4 weeks’ post-treatment)

TG: 10-week aerobic exercise intervention, twice per week, 90 min per session CG: usual care

SF-36 EORTC QLQ-C30 HADS Body Image Questionnaire;

Participants in the TG improved significantly over time with regard to anxiety (p = 0.03), depression (p = 0.05), and individual body image (p = 0.006)

At baseline and at 10 weeks Milne 2008

RCT

Moadel 2007

RCT

Mustian 2004

RCT

58 breast cancer survivors ([12 months’ post-treatment)

TG: 12-week aerobic exercise intervention, 3 times per week, 1 h per session

128 breast cancer survivors (*3 months’ post-treatment)

TG: 12-week yoga intervention, once per week, 90 min per session

31 breast cancer survivors (1 week– 2.5 years’ posttreatment)

TG: 12-week tai chi exercise intervention, 3 times per week, 1 h per session

FACT-B; At baseline and at 12 weeks

CG: waitlist control

CG: waitlist control

CG: psychosocial support, 3 times per week for 12 weeks

FACT-G; At baseline and at 12 weeks

FACIT-F Self-esteem by Rosenberg SelfEsteem Scale;

QOL increased in the TG from baseline to 12 weeks by 20.8 points compared to a decrease in the CG of 5.3 points (p \ 0.001) The control group had a greater decrease in social well-being compared with the intervention group after controlling for baseline social well-being and covariates (p \ 0.0001) Women in the TG demonstrated significant improvements in QOL, while women in the CG reported declines in QOL

At baseline and at 12 weeks

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Breast Cancer Table 1 continued Trial

Study design

Study participants

Intervention

Outcome measure and assessment points

Outcome/results

Ohira 2006

RCT

86 breast cancer survivors (C3 months’ post-treatment)

TG: 24-week aerobic exercise training, twice per week (time per session not reported) CG: usual care

Cancer Rehabilitation Evaluation System (CARES) shortform

The physical and psychosocial global QOL score improved in the TG compared with the CG (p = 0.006, p = 0.02, respectively)

CES-D; At baseline and at 24 weeks Payne 2008

Penttinen 2011

Pinto 2003

RCT

RCT

RCT

20 breast cancer survivors (posttreatment, time not reported)

573 breast cancer survivors (C1 month’s post-treatment)

24 breast cancer survivors (*12 months’ post-treatment)

TG: 14-week aerobic exercise intervention, 4 times per week, 20 min per session

Fatigue Scale

CG: usual care

CES-D;

TG: 48-week aerobic exercise intervention, once per week, 60 min per session CG: usual care

TG: 12-week supervised aerobic and anaerobic exercise program, 3 times per week, 50 min per session CG: waitlist control

Sleep Disturbance Scale At baseline and at 14 weeks EORTC QLQ-C30 FACIT-F BDI;

Effect of the exercise intervention on sleep scores was highly significant between groups: exercise group scores decreased significantly over time

The global QOL was lower than in general population compared women in the TG (69.4 vs. 74.7, p \ 0.001)

At baseline, at 6 months and at 12 months POMS Positive and Negative Affect Scale Body Esteem Scale;

Women in the TG improved significantly in body image versus the CG women. Reduction in distress was also noted in the TG, but this was non-significant

At baseline and at 12 weeks Pinto 2005

Rogers 2009

Saarto 2012

RCT

RCT

RCT

86 breast cancer survivors (posttreatment, time not reported)

TG: 12-week aerobic exercise intervention, 2–5 times per week, 10–30 min per session

41 breast cancer survivors ([24 months’ post-treatment)

TG: 12-week aerobic exercise intervention, 3–5 times per week (time per session not reported)

573 breast cancer survivors (C12 months’ post-treatment)

TG: 12-month aerobic exercise and resistance training intervention, once per week, 70–75 min per session

POMS; At baseline and at 12 weeks

CG: usual activities

CG: usual care

CG: usual care

FACT-G FACT-B FACT-F; At baseline and at 3 months EORTC QLQ-C30 EORTC QLQBR23 FACIT-F BDI; At baseline, at 6 months and at 12 months

Speck 2010

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RCT

234 breast cancer survivors ([36 months’ post-treatment)

There was a positive trend in intervention effects on overall mood and body esteem

TG: 52-week aerobic and anaerobic strength training intervention, twice per week, 90 min per session

Body Image and Relationships Scale (BIRS);

CG: usual care

At baseline, at 6 months and at 12 months

Differences favoring the TG were noted for aerobic fitness (p = 0.058) and social well-being (p = 0.03)

No significant between-group differences were observed in EORTC QLQ-C30, BR23, FACITF or BDI. But there was a linear relationship between increased physical activity and improved QOL (p = 0.006)

Significantly greater improvement in BIRS total score was observed from the baseline to 12 months in the TG versus the CG (12 vs. 2 %; p \ 0.0001)

Breast Cancer Table 1 continued Trial

Study design

Study participants

Intervention

Outcome measure and assessment points

Outcome/results

Sprod 2012

Pilot RCT, Parallel

19 breast cancer survivors ([1 month’s post-treatment)

TG: 12-week tai chi exercise intervention, 3 times per week, 60 min per session CG: standard support therapy with exercise control

SF-36

Physical functioning significantly improved in the tai chi group, but not in the control group There was a statistical trend toward an increase in insulin among the CG, but not among the tai chi group

Cortisol level Insulin level; At baseline and at 12 weeks

Changes in cortisol and insulin levels from pre- to postintervention were directly associated with changes in role limitations BDI beck depression inventory, BFI brief fatigue inventory, BMI body mass index, CES-D Center for Epidemiological Studies-Depression Scale, CG control group, EORTC QLQ-C30 European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, QLQ-BR23 Quality of Life Questionnaire-Breast, FACIT-F functional assessment of chronic illness therapy-fatigue, FACIT-Sp functional assessment of chronic illness therapy-spirituality, FACT-B functional assessment of cancer treatment-breast, FACT-F functional assessment of cancer treatment-fatigue, FACT-G functional assessment of cancer treatment-general, POMS profile of mood state, RCT randomized controlled trial, SF-36 MOS Short-Form 36 Survey, TG treatment group

Fig. 2 Risk of bias summary on the 25 included trials

the FACT-B, Fig. 5 shows that the weighted mean difference (WMD) was 5.72 (95 % CI 1.98, 9.46). For cancerspecific QOL domains measured by the EORTC QLQBR23, there were a total of six sub-scales (Fig. 6a–f), and only two domains (breast symptoms and arm symptoms) favored exercise interventions. In other words, exercise interventions showed trends in the direction of improving breast and arm symptoms for breast cancer survivors, but these effects were not statistically significant (breast symptoms: Z score = 1.12, p = 0.26; arm symptoms: Z score = 1.32, p = 0.19). Subgroup analyses of QOL changes in breast cancer survivors by intervention methods Based on intervention methods, four subgroup analyses were conducted. Figure 7a–d shows the SMDs of four types of exercise interventions on the QOL of breast cancer

survivors. The SMD of aerobic exercise on the QOL score changes was 0.53 (95 % CI 0.08, 0.99) (Fig. 7a). The SMD of aerobic combined with anaerobic exercise on the QOL score changes was 0.50 (95 % CI -0.21, 1.22) (Fig. 7b). The SMD of Yoga intervention on the QOL score changes was 0.42 (95 % CI 0.09, 0.75) (Fig. 7c). The SMD of Tai Chi intervention on the QOL score changes was 1.97 (95 % CI 0.31, 3.64) (Fig. 7d). Of 25 included trials, one study [25] reported the adverse effects related to exercise interventions, and this study found a higher rate of lymphedema in the exercise group than the comparison group.

Discussion This meta-analysis examined the pooled effects of exercise intervention on QOL in breast cancer survivors. Of the 25 trials, six were excluded from statistical pooling because they did not have enough data about changes in QOL scores. Of the 19 trials included in the meta-analysis, six reported consistent findings of positive effects of exercise intervention in overall QOL and QOL domains in breast cancer survivors. These 6 studies examined the effect of exercise intervention on general QOL, and the pooled results show a moderate to large effect (effect size = 0.70). The effect size of global QOL found by Duijts and colleagues’ review [2] was lower than the effect size in the current study. One possible explanation for this difference is that the study populations were different. The current study only included breast cancer survivors, while Duijts and

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Breast Cancer Table 2 Summary of meta-analysis results Comparison

Total scores or sub-scales

No. of studies

No. of subjects

Statistical method

Effect size

General QOL change By generic QOL scales (e.g., SF-36)

Total scores

6

373

SMD (IV, Random, 95 % CI)

0.70 (0.21, 1.19)

Total scores

10

1,073

SMD (IV, Random, 95 % CI)

0.38 (0.03, 0.74)

Total scores

6

388

WMD (IV, Random, 95 % CI)

5.72 (1.98, 9.46)

Body image

2

565

WMD (IV, Fixed, 95 % CI)

-1.30 (-2.13, -0.46)

Sexual functioning

2

565

WMD (IV, Random, 95 % CI)

-6.25 (-20.58, 8.08)

Cancer-specific QOL change By FACT-G or EORTC QLQ-C30 Cancer site-specific QOL change By FACT-B By EORTC BR-23

Future perspective

2

565

WMD (IV, Random, 95 % CI)

-4.41 (-11.33, 2.52)

Systematic therapy side effects

2

565

WMD (IV, Random, 95 % CI)

-1.77 (-9.79, 6.25)

Breast symptoms

3

725

WMD (IV, Random, 95 % CI)

8.93 (-6.75, 24.62)

Arm symptoms

3

725

WMD (IV, Random, 95 % CI)

4.64 (-2.24, 11.52)

WMD weighted mean difference, SMD standardized mean difference

Fig. 3 General QOL change

Fig. 4 Cancer-specific QOL by FACT-G or EORTC QLQ-C30

Fig. 5 Cancer site-specific QOL by FACT-B

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Fig. 6 a Cancer site-specific QOL by EORTC BR-23 of body image. b Cancer site-specific QOL by EORTC BR-23 of sexual functioning. c Cancer site-specific QOL by EORTC BR-23 of future perspective. d Cancer site-specific QOL by EORTC BR-23 of systematic therapy

side effects. e Cancer site-specific QOL by EORTC BR-23 of breast symptoms. f Cancer site-specific QOL by EORTC BR-23 of arm symptoms

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Fig. 7 a Effects of QOL score changes by aerobic exercise intervention only. b Effects of QOL score changes by aerobic combined with anaerobic exercise interventions. c Effects of QOL

score changes by Yoga interventions. d Effects of QOL score changes by Tai Chi interventions

colleagues’ study included both breast cancer patients and survivors. Furthermore, Duijts and colleagues’ [2] review examined the pooled effects of global QOL in combination with generic and cancer-specific QOL measures. The pooled results of 10 studies involving 1,073 subjects showed a small to moderate effect (effect size = 0.38) of exercise interventions on cancer-specific QOL. The effect

size of cancer-specific QOL in this study was lower than that of a meta-analysis conducted by McNeely and colleagues [14]. McNeely and colleagues examined the effect of exercise intervention on breast cancer patients and survivors measured by the FACT-G and reported a WMD of 4.58 (95 % CI 0.34, 8.80) among 194 subjects [14]. While there are differences in the study populations, the sample

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size in the current study used to generate the pooled effect of cancer-specific QOL was far larger (n = 1,073 vs. n = 194). For the cancer-specific QOL domains, two domains showed positive improvement, but they were not statistically significant. The exercise intervention programs included in the 25 trials varied greatly in their mode, duration, frequency, and time per session. These intervention variations minimize the applicability of the findings to clinical settings. Hence, it is important to determine what types of exercise program are optimal for the improvement of QOL of breast cancer survivors. In addition, the nature of exercise intervention delivery is that it is difficult to blind research participants and intervention deliverers. However, future rigorous trials should attempt to blind the outcome assessors to minimize potential methodological bias. By subgroup analyses based on intervention methods, single type of exercise intervention by general aerobic exercise, Yoga, or Tai Chi had statistically significant differences in the QOL score changes in breast cancer survivors. From Fig. 7b, as the 95 % CI of SMD crossed 0, the effect of aerobic combined with anaerobic exercise interventions in the QOL score changes should not be considered statistically significant. Future research needs to examine whether single type of exercise intervention is better than multiple types of exercise intervention on improving the QOL of breast cancer survivors. While exercise interventions demonstrate positive effects on QOL of breast cancer survivors, some demographic factors may affect the QOL outcome evaluation among this study population. Age may influence the potential to evaluate the effect of exercise intervention on QOL among breast cancer survivors, as increasing age may be related to the likelihood of sedentary behaviors [45]. Previous regular exercise history or baseline physical activity level was a significant predictor of adherence to exercise intervention [46]. Other studies found that breast cancer survivors from racially and ethnically diverse populations have lower levels of exercise and higher rates of obesity that are generally associated with poorer QOL [47]. Ashing-Giwa and Lim [48] indicated that ethnic variations existed in QOL according to socioeconomic status. Higher socioeconomic status groups expressed better QOL, as socioecologic stress was the most important factor contributing to lower level of QOL among breast cancer survivors. Therefore, culturally sensitive exercise interventions are needed to develop for improving the QOL of ethnic breast cancer survivors. In terms of the adverse effects of exercise interventions, one study [25] reported that there was a higher rate of lymphedema in the exercise group, although Courneya et al. commented that it was not clear whether the onset of lymphedema was due to the physical activity. Therefore,

there is a need to explore the adverse effects of exercise among breast cancer survivors in future research. Limitations of this meta-analysis should be noted. Selective publishing and reporting bias is well-documented problems that affect virtually all systematic reviews and meta-analyses, and it can lead to overestimation of the positive effects of exercise interventions. In addition, most of the studies in this meta-analysis have a high risk of bias, so more rigorous trials with higher standards of trial methodology are needed to determine the effect of exercise interventions on QOL of cancer survivors.

Conclusion This study provides updated findings that support the idea that exercise interventions have statistically significant effects on overall QOL in breast cancer survivors, as well as positive trends for cancer site-specific QOL domains (breast and arm symptoms). Based on the benefits of exercise interventions for breast cancer survivors, health care professionals could consider adopting exercise interventions as an integral component of the management of QOL in breast cancer survivors. Exercise intervention programs in the current review varied greatly. Further research is urgently needed to determine the essential attributers of exercise (mode, duration, frequency, and time per session) for optimal effects on the QOL of breast cancer survivors. Conflict of interest of interest.

The authors declare that they have no conflict

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